There is an important need for novel therapies to treat heart failure. The use of pharmacological therapies has improved survival in heart failure patients. Additionally, new mechanical assist devices and xenotransplantation approaches are currently being developed yet mortality remains high, with more than 50% of all patients succumbing within 5 years of initial diagnosis. The utility of cardiac transplantation is limited by shortage of donor hearts, the complications of immunosuppression, and the failure of grafted organs.
The molecular basis for the syndrome of congestive heart failure is a lack of stem cells in the myocardium and the inability of the damaged heart cells to undergo repair or divide. The idea of transplanting single cells instead of entire organ has a number of attractive attributes and is dependent on an ever expanding understanding of molecular basis of skeletal myogenesis.
Heart failure remains a significant public health problem in contemporary cardiology. Prevalence of heart failure, estimated between 1% and 4% of the population, increases exponentially with age, so that current demographic trends in industrialized nations predict an increase in the number of patients with heart failure during coming decades as the populations of these countries grow older.
Heart failure is associated with significant morbidity, a high incidence of complications, frequent hospitalization, and rising healthcare costs. Mortality and morbidity caused by cardiac insufficiency are increasing at a time when the overall cardiovascular death rate is on the decline. In the United States alone, an estimated 2.5-4 million individuals have a diagnosis of “congestive heart failure”, and an additional 400,000-500,000 new cases are diagnosed annually.
A large proportion of the end stage heart failure patients need a therapeutic approach other than the current standard modalities, due to the restricted number of heart donors for heart transplantation and the high cost and drawbacks of mechanical assist devices. Approximately, 25% of patients included in waiting lists for heart transplantation die, due to the limited donor availability.
Congestive cardiac failure is caused by a decrease in myocardial contractility due to mechanical overload or by an initial defect in the myocardial fiber. The alteration in diastolic function is inextricably linked with the pathophysiology of cardiac insufficiency. Despite a widely varying and diverse etiology of congestive cardiac failure (e.g. ischemic or idiopathic dilated cardiomyopathies), the pathophysiology is to a great extent constant. The predominant factor is the alteration of myocardial contractility. This contractility defect causes an elevation of the ventricular wall tension resulting in a progressive decline in the contractile state of the myocardial fibers.
Heart failure involves in many cases defects of the heart conduction system as well as depressed myocardium contractility together with enlarged ventricular cavities. Heart failure patient death is either due to pump failure or to arrhythmia (sudden death—ventricular tachycardia/ventricular fibrillation.
Cell transplantation strategies have been designed to replace damaged myocardial cells with cells that can perform cardiac work. The cellular cardiomyoplasty procedure consists in transplanting cultured satellite cells (myoblasts), originated from a skeletal muscle biosy of leg or arms of the same individual, to the sick myocardium. Satellite cells are mononucleated cells situated between the sarcolemma and the basal lamina of differentiated muscle fibers. They are thought to be responsible for postnatal growth, muscle fiber repair and regeneration. Another approach for cellular cardiomyoplasty consists in the utilization of bone marrow stem cells, autologous or foetal cardiomyocytes, or smooth muscle cells.
One of the problems limiting hemodynamic benefits of cellular cardiomyoplasty is that even if the myoblasts survived after implantation, functionally this cells cannot contract spontaneously, hence, they do not contribute to improve regional myocardial contractility. Mechanical and electrical coupling of the transplanted myoblasts with the cardiomyocytes is still not clear.